Acknowledgments: The authors thank Dr. Marcia Levenstein, Dr. Lichen Teng, and Paul Schwartz of Pfizer, Inc., for performing statistical analyses; Dr. David Bruckner and the staff of the UCLA clinical microbiology laboratories for technical assistance; Ed Arriola and the staff of the UCLA pharmacy service for administrative assistance; and Katharine Fry for preparation of the manuscript. They also thank the UCLA liver transplant physicians and nurses for their assistance and for care of patients during the study.

Grant Support: By a research grant from Pfizer, Inc., the Joanne Barr Foundation, and the Dumont Foundation.

Abstract

Background:

Among persons who receive solid organ transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective.

Objective:

To evaluate the efficacy and safety of prophylactic fluconazole in liver transplant recipients.

Design:

Randomized, double-blind, placebo-controlled trial.

Setting:

University-affiliated transplantation center.

Patients:

212 liver transplant recipients who received fluconazole (400 mg/d) or placebo until 10 weeks after transplantation.

Fungal colonization increased in patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003).